The present disclosure relates generally to medical treatments. More specifically, the present disclosure relates to solutions for peritoneal dialysis therapy.
Due to disease or other causes, a person's renal system can fail. In renal failure of any cause, there are several physiological derangements. The balance of water, minerals and the excretion of daily metabolic load are no longer possible in renal failure. During renal failure, toxic end products of nitrogen metabolism (e.g., urea, creatinine, uric acid, and others) can accumulate in blood and tissues.
Kidney failure and reduced kidney function have been conventionally treated with dialysis therapies. Dialysis removes waste, toxins and excess water from the body that would otherwise have been removed by normal functioning kidneys. Dialysis treatment for replacement of kidney functions is critical to many people because the treatment is life saving. One who has failed kidneys could not continue to live without replacing at least the filtration functions of the kidneys.
In peritoneal dialysis (“PD”), the osmotic agent is used in the dialysis solution to maintain the osmotic gradient required to cause transport of water and toxic substances across the peritoneum into the dialysis solution. One of the difficulties encountered in PD therapy is providing a dialysate that includes a suitable osmotic agent. Achieving a sufficient osmotic gradient is required.
Presently, the osmotic agent that is most commercially used is glucose. Glucose is fairly safe and is readily metabolized if it enters the blood. However, one of the problems with glucose is that it is readily taken up by the blood from the dialysate. Because glucose crosses the peritoneum so rapidly, the osmotic gradient is dissipated within two to three hours of infusion. This can reverse the direction of ultrafiltration, causing water to be reabsorbed from the dialysate toward the end of the time allowed for the exchange.
Glucose also presents other problems for dialysis treatment. For example, because glucose is taken up so rapidly by the blood, it can represent a large proportion of the patient's energy intake. While this may not significantly affect a non-diabetic patient, it can represent a severe metabolic burden to a patient whose glucose tolerance is already impaired. Glucose can also cause problems with respect to hyperglycemia and obesity. Finally, heat sterilization of glucose can result in unwanted glucose degradation products.
Ultrafiltration characteristics of PD solutions can be improved during long dwells by replacing glucose with large molecular weight substances such as glucose polymers. Dialysis solutions containing certain glucose polymers, i.e., icodextrin, are commercially available and have been found to be useful in treating patients with end stage renal disease.
Summary
The present disclosure is directed to PD solutions including a glucose polymer and methods of using the dialysis solutions. In a general embodiment, the PD solutions include one or more glucose polymers having specific characteristics and in an amount that provides an increased ultrafiltration (“UF”) fluid volume for a given amount of carbohydrate (“CHO”) absorbed compared to conventional dialysis solutions containing icodextrin as the active pharmaceutical ingredient (“API”). The increased UF fluid volume for a given amount of CHO absorbed is obtained by providing specific combinations of weight-average molecular weight (“Mw”), polydispersity (“PolyD”) index (e.g., Mw/Mn) and concentration (e.g., by weight/volume percent (“w/v”)) of the glucose polymers in the dialysis solutions. The dialysis solutions can be sterilized using any suitable sterilizing methods.
In any embodiments of the dialysis solutions disclosed herein, the PD solutions can include one or more additional dialysis components such as buffers, electrolytes or a combination thereof. The buffer can be bicarbonate, lactate, pyruvate, acetate, citrate, amino acids, peptides, an intermediate of the KREBS cycle or a combination thereof. The electrolytes can be calcium, magnesium, sodium, potassium, chloride or a combination thereof.
In an alternative embodiment, the present disclosure provides a method of preparing a PD solution. The method includes selecting a specific Mw, a PolyD index and a w/v concentration of the glucose polymer to be used in the dialysis solution, and providing the glucose polymer at the specified PolyD index, molecular weight and w/v concentration in a dialysis solution.
In yet another embodiment, the present disclosure provides a method of providing PD to a patient in need of same. The method includes selecting a specific Mw, a PolyD index and a w/v concentration of the glucose polymer to be used in the dialysis solution, providing the glucose polymer at the specified PolyD index, molecular weight and w/v concentration in a dialysis solution, and administering the dialysis solution to the patient.
An advantage of the present disclosure is to provide an improved PD solution including glucose polymers.
Another advantage of the present disclosure is to provide a PD solution capable of providing an increased UF fluid volume for a given amount of CHO absorbed compared to conventional dialysis solutions containing icodextrin as the API.
Still another advantage of the present disclosure is to provide a method of making an improved PD solution containing a glucose polymer.
Yet another advantage of the present disclosure is to provide an improved method of administering a PD solution containing a glucose polymer.
Additional features and advantages are described herein, and will be apparent from the following Detailed Description and the figures.